Cardiotonic agents. 1-Methyl-7-(4-pyridyl)-5,6,7,8-tetrahydro-3(2H)-isoquinolinones and related compounds. Synthesis and activity

Abstract

A series of 1-methyl-7-(4-pyridyl)-5,6,7,8-tetrahydro-3(2H)-isoquinolinones and related compounds were synthesized and evaluated for positive inotropic activity. Most members of this series exerted a dose-dependent increase in myocardial contractility in the dog acute heart failure model, whereas they caused only slight changes in heart rate and blood pressure. Several derivatives, especially those with cyano, acetyl, and ethyl substituents at the 4-position, were more potent than milrinone, which was used as a reference. 4-Acetyl-1-methyl-7-(4-pyridyl)-5,6,7,8-tetrahydro-3(2H)-isoquinolinone (MS-857) is one of the most potent positive inotropic agents in this series.

Photoinduced Charge Separation in Cyclohexylidene‐Based Donor−(σ‐Bridge)−Acceptor Compounds − Building Blocks for Materials

“…The syntheses of ketone 8 and D1 are depicted in Scheme . In a broad sense, the synthetic route to 8 follows the route described by Kaiho et al21 The Grignard reagent of 4‐bromo‐ N , N ‐dimethylaniline (prepared either by a dry‐stirring method22 or by application of ultrasound21) was added to cyclohexanone ( 9 ) and ketone 4 , to form 10 and 5 , respectively. These alcohols were dehydrated under acidic conditions to form 11 and 6 .…”

Divergent enantioselective synthesis of hapalindole-type alkaloids using catalytic asymmetric hydrogenation of a ketone to construct the chiral core structure

“…4 f The C12- epi -quaternary stereocenter was constructed by controlling the stereochemistry of the acylation–methylation sequence ( Scheme 5 ). Specifically, treatment of optically active cycloketone (+)- 14 with LiHMDS and trapping with N -acetylimidazole 18 yielded diketone (+)- 20 in 70% yield. α-Methylation of (+)- 20 with MeI in the presence of K 2 CO 3 afforded 91% yield of diketone (+)- 21 , which has a quaternary carbon center.…”

Design, synthesis and biological evaluation of novel 1-methyl-3-oxo-2,3,5,6,7,8-hexahydroisoquinolins as potential EZH2 inhibitors

“…The compounds described in this study were synthesized according to Scheme 1. Briey, treatment of ketone 1 with ethyl acetate under sodium hydride 24 or acetyl chloride under LDA 25 afforded 1,3-diones 2. Then the key building blocks pyridine-2-(1H)-ones 3 were prepared by treating 1,3-diones with cyanoacetamide in the presence of triethylenediamine (DABCO) in reuxing ethanol.…”